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Andria F. Church, PharmD, BCPS, BCPP
Assistant Professor of Pharmacy Practice
Palm Beach Atlantic University – Gregory School of Pharmacy
West Palm Beach, FL

This session is available at https://cpnp.org/ed/course/updates-and-advances-antipsychotic-induced-metabolic-adverse-events

During Virtual CPNP 2020, Dr. Correll gave an excellent presentation on antipsychotic-induced metabolic adverse events. His presentation was rich with valuable tables, graphs, and figures, so slide numbers have been included within the below text for your convenience and easy referencing. Here are some of the presentation highlights.

Metabolic syndrome is a risk constellation that includes five key components: waist circumference, blood pressure, fasting blood glucose, fasting HDL, and fasting triglycerides. While an individual must meet at least three out of five criteria to have metabolic syndrome, an abnormality in any single parameter should not be ignored. Recall that treatment with pharmacological agents for hypertension, diabetes, and/or dyslipidemia also constitutes a check-mark for the associated criteria. Dr. Correll also mentions that BMI can be used in place of waist circumference in certain circumstances. A key aspect regarding risk factors is that we now know there are additional components that should be included in a more modern and up to date definition of metabolic syndrome. These include inflammation, endothelial dysfunction, and impaired thrombolysis (slide 22). Of course, there are additional factors (e.g., age, family history, genetics, etc.) that play a role in insulin resistance and atherosclerosis as well.

Individuals with mental illness are at higher risk of having less healthy lifestyle behaviors and risk factors for cardiovascular death (slide 9). Certain lifestyle factors such as smoking, increased alcohol use, less physical activity, and a less healthy diet (e.g., lower in fruits, grains, vegetables, etc.) can lead to other cardiovascular risk factors, like high blood pressure. The underlying mental illness may also contribute to a person’s impaired motivation, ability to engage in physical activity, and be adherent to regimens. Therefore, when combining factors of mental illness, lifestyle behaviors, and psychotropic treatment, this can result in increased relative risk and prevalence of modifiable risk factors for cardiovascular illness and death. On slide 10, Dr. Correll cites a study that illustrates how this applies to both schizophrenia and bipolar disorder compared to the general population.

Aside from educating and assisting patients to reduce their weight or keep it down, we need to remain mindful of antipsychotics that can be more metabolically toxic and avoid these agents earlier in treatment. These medications should be reserved after treatment failure(s) with less metabolically toxic agents (slide 24). When we consider antipsychotic treatment options, no agent is entirely metabolically neutral, which is why we must assess the risk profiles (slide 28). On slide 44 Dr. Correll includes a heat map of 18 different antipsychotics and their associated cardiometabolic risk profiles; a great table to review. In the same vein, we must also be diligent in psychotropic medication monitoring. Via thorough monitoring of side effects and laboratory parameters, we can track trends and intervene more readily.

In a 2019 meta-analysis and meta-review (slides 48-49), investigators looked at the impact of both non-pharmacological and pharmacological interventions to improve physical health outcomes in those with schizophrenia. Both individual lifestyle counseling and exercise interventions had what investigators deemed a “large effect size” for weight change. The IMPACT trial (slide 53-56) evaluated overweight or obese youth with severe mental illness to see which intervention influenced weight: 1) healthy lifestyle instruction (HLI) alone, 2) HLI + switching to a lower risk antipsychotic, or 3) HLI + metformin. Those who received HLI alone continued gaining weight. In the other two groups, there was no significant difference. Overall, the current medication recommendations for antipsychotic-induced weight gain are metformin, topiramate, or augmentation with aripiprazole. Other metabolic abnormalities should be treated as clinically indicated (slide 57).

Some key conclusions from Dr. Correll’s presentation are: 1) utilize non-pharmacological interventions first or in combination with pharmacological agents for metabolic issues, 2) pharmacological interventions for the treatment of metabolic syndrome in the mentally ill have not been thoroughly studied, 3) pharmacological agents have varying efficacy and effect sizes depending on the metabolic syndrome component they are treating, and 4) the pharmacological agents that have the greatest efficacy evidence for certain metabolic syndrome parameters are metformin, topiramate, switching to an antipsychotic with lower metabolic risk, and also GLP-1 agonists.

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